Diabetes is a leading cause of disease, disability, and death in modern societies. In the U.S., approximately 10% of the population or 30 million people have diabetes. Worldwide, the prevalence is approximately 400 million, and is projected to increase to 600 million by 2035. In addition to the heavy health burden of diabetes and its complications, the financial costs are enormous: $245 billion per year in the U.S. and $1.3 trillion per year worldwide.
Type 2 is the major form of diabetes, accounting for more than 90% of all cases. Type 2 diabetes does not have a sudden onset, but develops insidiously over many years or even decades. The earliest stage consists of insulin resistance, often accompanied by lipid abnormalities and a pro-inflammatory, pro-coagulation state. Insulin resistance is associated with obesity, which causes adipose tissue inflammation. A healthy pancreas attempts to compensate for insulin resistance by secreting more insulin into the blood. This compensatory response keeps blood glucose levels in the normal range (<100 mg/dL). Thus, early insulin resistance is not detected by fasting glucose levels, the primary diabetes screening test used in medical clinics.
Over time, the heavy secretory demand caused by insulin resistance damages the insulin-secreting beta cells of the pancreas. Once insulin secretory capacity diminishes by 30-50%, the pancreas can no longer keep up, and fasting blood glucose levels become elevated. This stage is known as prediabetes, defined by fasting glucose levels of 100-124 mg/dL or hemoglobin A1C levels of 5.7-6.4%. In addition, elevated fasting glucose is one of five clinical criteria for metabolic syndrome, a condition that reflects poor metabolic health. Individuals with metabolic syndrome have a five-fold increased risk for type 2 diabetes and a 2-3-fold increased risk for atherosclerotic cardiovascular disease. Like prediabetes, the clinical criteria for metabolic syndrome fail to detect early-stage insulin resistance, where damage to the pancreas begins.
There are blood tests that, in principle, could be used to detect early-stage insulin resistance and its associated metabolic abnormalities. Examples include fasting insulin, lipid profiles, C-reactive protein, and others. However, the collection of multiple blood tests or blood panels is too expensive for routine screening of metabolic health. Health insurance companies do not cover the cost of metabolic panels for asymptomatic individuals with normal fasting glucose levels.
To overcome this barrier, a blood test has been developed that assesses metabolic health. PCT Application PCT/US2016/016906, filed Feb. 2, 2016, titled “Methods and tools for diagnosing insulin resistance and assessing health status using NMR relaxation times for water” describes a means for developing an inexpensive blood test for frontline health screening and monitoring. The test can be used for the diagnosis of insulin resistance syndrome, an early metabolic abnormality that leads to type 2 diabetes. The test analyzes the spin relaxation times (T2 and/or T1 or surrogates of T2 and/or T1) of water in plasma, serum, or whole blood using nuclear magnetic resonance (NMR). The blood samples however, must be obtained using a conventional needle stick or finger prick. PCT Application PCT/US2016/016906 is incorporated herein by reference in its entirety.
Nuclear Magnetic Resonance (NMR) techniques are used for various medical and analytical purposes. The term “NMR” can refer to a variety of diagnostic methods. There are many types of NMR methods and instruments and thousands of distinct NMR experiments have been conducted.
The three main categories are NMR spectroscopy, NMR imaging (currently known as magnetic resonance imaging or MRI), and NMR relaxometry. Spectroscopy generates molecular signatures of an atomic resolution, and imaging generates anatomical images with spatial resolution. These two categories of NMR usually require high-field or large bore magnets and complex, expensive instrumentation. Although based on the same fundamental physics, NMR relaxometry involves different instrumentation, methods, and derived measurables, compared with spectroscopy and imaging. Thus, different kinds of NMR are used in somewhat related but distinct areas of medical diagnosis, imaging, and treatment.
Another NMR relaxometry-based blood test is described in U.S. application Ser. No. 13/839,420, filed Mar. 15, 2013, titled “NMR method for monitoring changes in the core of lipoprotein particles in metabolism and disease.” Unlike the PCT application referenced above, this application describes a method for directly measuring the properties of protein and lipoprotein elements in a sample, typically blood, rather than measuring water. The method includes the placing of a small volume of a blood sample into an NMR instrument tuned to measure a particular nucleus, applying a series of radiofrequency pulses with intermittent delays in order to measure spin-spin and/or spin-lattice relaxation time constants. While this represents an advance in NMR relaxometry-based blood testing, it also requires collection of a blood sample via a standard blood draw or needle stick. U.S. application Ser. No. 13/839,420 is incorporated herein by reference in its entirety.
In general, NMR imaging and spectroscopy methods are too expensive and too cumbersome to be carried out in outpatient point-of-care settings, such as a primary care practitioner's office. Moreover, current NMR relaxometry methods require blood samples by venipuncture or finger prick.
Further, when a particular test is difficult to carry out, must be carried out off-site, will take significant time to complete, or any combination thereof, the use of that test tends to be less frequent than tests that can be carried out quickly and easily at a location (e.g., a physician's office, small clinic, or hospital) where patients are typically located.
Accordingly, there is an unmet need for testing methods that can be used to identify metabolic health and help identify patients at risk for diabetes. By extension, a need exists for faster, simpler, and less expensive means for identifying and measuring characteristics that correlate to metabolic health.